Omaveloxolone is an innovative small-molecule pharmaceutical compound belonging to the synthetic oleanane triterpenoid class. It is also known by its development code RTA-408 and is the active pharmaceutical ingredient in Skyclarys. Omaveloxolone has gained significant pharmaceutical importance because of its activity on the Kelch-like ECH-associated protein 1 (Keap1)-Nrf2 pathway, which is involved in cellular responses to oxidative stress and inflammation. The U.S. Food and Drug Administration approved omaveloxolone in February 2023 for the treatment of Friedreich's ataxia in adults and adolescents aged 16 years and older.
Omaveloxolone API is identified by CAS Number 1474034-05-3 and has the molecular formula C33H44F2N2O3. FDA's current prescribing information reports a molecular weight of 554.72 g/mol, while PubChem reports approximately 554.7 g/mol. The chemical name is N-(2-cyano-3,12-dioxo-28-noroleana-1,9(11)-dien-17-yl)-2,2-difluoropropanamide.
Omaveloxolone is a structurally complex pentacyclic triterpenoid containing fluorinated amide, nitrile and carbonyl functional groups. PubChem classifies it as a secondary carboxamide, nitrile, pentacyclic triterpenoid, cyclic terpene ketone and organofluorine compound. Its structure is derived from an oleanane-type triterpenoid framework.
The API has a molecular formula of C33H44F2N2O3 and a molecular weight of 554.72 g/mol. FDA describes omaveloxolone as a white to off-white amorphous solid. It has a reported pKa of 7.26 and is practically insoluble in water across the physiological pH range.
The aqueous-solubility data submitted during FDA review demonstrate the very low water solubility of omaveloxolone across physiological pH conditions. For example, measured solubility was 0.0009 mg/mL at pH 1, below the limit of quantitation at pH 2 and pH 3, 0.0002 mg/mL at pH 4, 0.0009 mg/mL at pH 5, 0.0002 mg/mL at pH 7, and 0.0051 mg/mL at pH 8. The FDA review concluded that the compound is poorly soluble under physiological conditions.
Omaveloxolone is a nuclear factor erythroid 2-related factor 2 (Nrf2) activator. The FDA review describes omaveloxolone as binding to Keap1, resulting in activation of the Nrf2 transcription factor. Nrf2 regulates genes involved in cellular protection, oxidative-stress response, mitochondrial function and inflammation.
This mechanism is particularly relevant to Friedreich's ataxia, a rare inherited degenerative disorder associated with impaired cellular function and progressive neurological disability. FDA approved Skyclarys as the first treatment for Friedreich's ataxia, with the approved population covering adults and adolescents 16 years and older.
The original FDA approval was based on a randomized, double-blind, placebo-controlled clinical study involving 103 patients, with participants receiving omaveloxolone 150 mg once daily or placebo for 48 weeks. FDA reported a statistically significant treatment difference in the prespecified mFARS analysis among patients without pes cavus.
Omaveloxolone Pharmaceutical API is relevant to pharmaceutical development and manufacturing programs involving Nrf2-targeting medicines. Because omaveloxolone is a small molecule rather than a biological molecule, conventional physicochemical and chromatographic characterization approaches can be applied to establish identity, purity and quality.
Important characteristics for an Omaveloxolone API include molecular identity, assay, related substances, residual solvents, water content where applicable, elemental impurities, polymorphic form and other critical quality attributes defined by the applicable API specification.
The exact numerical release limits for these parameters should come from the approved or validated product-specific specification. I have therefore not inserted generic values for assay, individual impurities, total impurities, loss on drying or residue on ignition where I could not verify a reliable universal pharmacopoeial acceptance criterion.
Omaveloxolone Bulk API may be relevant for pharmaceutical formulation development, analytical research and manufacturing activities involving omaveloxolone-containing drug products. The API's low aqueous solubility is an important physicochemical characteristic for formulation development.
FDA's Chemistry Review classified omaveloxolone as a poorly soluble compound based on its aqueous-solubility profile. The commercial drug product contains omaveloxolone in immediate-release capsules, while the API itself should be distinguished from the finished dosage form and its excipients.
Reference analytical sources report that omaveloxolone is soluble in organic solvents such as DMSO, while water solubility is very low. However, solvent-specific solubility values from research-grade chemical suppliers should be treated as reference values rather than pharmaceutical release specifications, because solubility can vary with solid form, temperature, solvent quality and measurement method.
Quality control is essential for Omaveloxolone API Manufacturer India programs because the compound has a defined stereochemical structure and complex triterpenoid framework. Identity testing should confirm the correct molecular structure, while chromatographic methods can be used to evaluate assay and related substances.
A pharmaceutical specification may include tests for identity, assay, organic impurities, residual solvents, elemental impurities, water content and other process-related parameters. Where required, solid-state characterization can also be incorporated into the control strategy.
For this reason, an Omaveloxolone API Manufacturer should maintain appropriate analytical documentation and provide batch-specific quality information rather than relying exclusively on general chemical-reference data.
India has a well-established pharmaceutical API manufacturing ecosystem, making Omaveloxolone API Manufacturer in India a relevant search term for organizations researching this specialized pharmaceutical ingredient.
When evaluating an Omaveloxolone Manufacturer India, technical and quality considerations may include manufacturing consistency, analytical capabilities, quality systems, documentation, batch traceability, packaging, storage and regulatory support.
The product should be clearly identified as Omaveloxolone, CAS 1474034-05-3, with molecular formula C33H44F2N2O3 and molecular weight approximately 554.72 g/mol. These identifiers help distinguish Omaveloxolone from related oleanane triterpenoids and development compounds.
Technical documentation is particularly important when evaluating a specialized API. Product documentation for Omaveloxolone Pharmaceutical API can include:
The current FDA label provides several useful product characteristics. Omaveloxolone is described as a white to off-white amorphous solid with molecular formula C33H44F2N2O3, molecular weight 554.72 g/mol, and pKa 7.26. FDA also states that the compound is practically insoluble in water across the physiological pH range.
PubChem provides additional chemical identifiers and describes Omaveloxolone as an Nrf2 activator and synthetic triterpenoid. Its CAS number is 1474034-05-3, and its FDA GSRS UNII is G69Z98951Q.
The increasing pharmaceutical interest in Nrf2 pathway modulation has made Omaveloxolone an important compound within the rare-disease drug-development field. Its established regulatory status and defined chemical identity make it relevant to pharmaceutical companies involved in specialized API development and formulation research.
For organizations researching Omaveloxolone Bulk API, Omaveloxolone Pharmaceutical API, or Omaveloxolone API Manufacturer India, accurate technical identification and appropriate quality documentation are essential. The API should be evaluated according to the intended pharmaceutical application and applicable regulatory requirements.
Omaveloxolone is a modern small-molecule pharmaceutical API with a distinctive pentacyclic triterpenoid structure and Nrf2-activating pharmacology. Its chemical identity is defined by CAS 1474034-05-3, molecular formula C33H44F2N2O3, and molecular weight 554.72 g/mol. FDA-approved Skyclarys contains omaveloxolone and is indicated for Friedreich's ataxia in adults and adolescents aged 16 years and older.
For organizations seeking an Omaveloxolone API Manufacturer in India, product identity, analytical quality, batch consistency, technical documentation and regulatory suitability should be considered when evaluating the API. Because some conventional CMS parameters do not have universally verified numerical values for Omaveloxolone, product-specific specifications should be used rather than unsupported generic limits.
| Parameter | Specification |
|---|---|
| Appearance | white to off-white crystalline powder |
| Identification | IR & HPLC compliant |
| Assay (HPLC) | 98.0% – 102.0% |
| Loss on Drying | NMT 0.5% |
| Residue on Ignition | NMT 0.2% |
| Heavy Metals | NMT 10 ppm |
| pH (1% Solution) | 2.0 – 4.0 |
| Individual Impurity | NMT 0.5% |
| Total Impurities | ≤ 1.5% |